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Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy <jats:italic>in vitro<\/jats:italic>. The <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> effects and mechanisms of acrolein on myogenesis and the <jats:italic>in vivo<\/jats:italic> effect of acrolein on muscle wasting still remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C2C12 myoblasts were used to assess the effects of low\u2010dose acrolein (0.125\u20131\u00a0\u03bcM) on myogenesis <jats:italic>in vitro<\/jats:italic>. Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5\u00a0mg\/kg) for 4\u00a0weeks with or without glycerol\u2010induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Non\u2010cytotoxic\u2010concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1\u00a0\u03bcM, 66.25% and 46.25% control, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The protein expression for myogenesis\u2010related signalling molecules (myogenin and phosphorylated Akt: 0.5 and 1\u00a0\u03bcM, 85.15% and 51.52% control and 62.63% and 56.57% control, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and myosin heavy chain (MHC: 0.5 and 1\u00a0\u03bcM, 63.64% and 52.53% control, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) were decreased in acrolein\u2010treated myoblasts. Over\u2010expression of the constitutively active form of Akt in myoblasts during differentiation prevented the inhibitory effects of acrolein (1\u00a0\u03bcM) on myogenesis (MHC and myogenin protein expression: acrolein with or without constitutively active Akt, 64.65% and 105.21% control and 69.14% and 102.02% control, respectively, <jats:italic>n<\/jats:italic>\u00a0=\u00a05, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Oral administration of acrolein for 4\u00a0weeks reduced muscle weights (5\u00a0mg\/kg\/day: 65.52% control, <jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and cross\u2010sectional area of myofibers in soleus muscles (5\u00a0mg\/kg\/day: 79.92% control, <jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) with an up\u2010regulation of atrogin\u20101 and a down\u2010regulation of phosphorylated Akt protein expressions. Acrolein retarded soleus muscle regeneration in a glycerol\u2010induced muscle regeneration mouse model (5\u00a0mg\/kg\/day: 49.29% control, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Acrolein exposure reduced muscle endurance during rotarod fatigue performance in mice with or without glycerol\u2010induced muscle injury (5\u00a0mg\/kg\/day without glycerol: 30.43% control, <jats:italic>n<\/jats:italic>\u00a0=\u00a04, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Accumulation of acrolein protein adducts could be detected in the soleus muscles of acrolein\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low\u2010dose acrolein significantly inhibited myogenic differentiation <jats:italic>in vitro<\/jats:italic>, which might be through inhibition of Akt signalling. Acrolein induced muscle wasting and retarded muscle regeneration in mice. These results suggest that acrolein may be a risk factor for myogenesis and disease\u2010related myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12362","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T11:18:04Z","timestamp":1540984684000},"page":"165-176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass"],"prefix":"10.1002","volume":"10","author":[{"given":"Huang\u2010Jen","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Chia","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Pediatrics, College of Medicine National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Cheng","family":"Chan","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Geriatrics and Gerontology, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Yuan","family":"Chiu","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Health, College of Public Health National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing\u2010Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Toxicology, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Pediatrics, College of Medicine National Taiwan University Hospital  Taipei Taiwan"},{"name":"Department of Medical Research China Medical University Hospital, China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100481"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100279"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu233"},{"key":"e_1_2_8_5_1","unstructured":"Agency for Toxic Substances and Disease Registry.Toxicological profile for acrolein.2007. 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